Immune microenvironment characterisation and dynamics during anti-HER2-based neoadjuvant treatment in HER2-positive breast cancer
Por:
Griguolo G, Serna G, Pascual T, Fasani R, Guardia X, Chic N, Pare L, Pernas S, Munoz M, Oliveira M, Vidal M, Llombart-Cussac A, Cortes J, Galvan P, Bermejo B, Martinez N, Lopez R, Morales S, Garau I, Manso L, Alarcon J, Martinez E, Villagrasa P, Prat A, Nuciforo P
Publicada:
19 mar 2021
Resumen:
Despite their recognised role in HER2-positive (HER2+) breast cancer (BC), the composition, localisation and functional orientation of immune cells within tumour microenvironment, as well as its dynamics during anti-HER2 treatment, is largely unknown. We here investigate changes in tumour-immune contexture, as assessed by stromal tumour-infiltrating lymphocytes (sTILs) and by multiplexed spatial cellular phenotyping, during treatment with lapatinib-trastuzumab in HER2+ BC patients (PAMELA trial). Moreover, we evaluate the relationship of tumour-immune contexture with hormone receptor status, intrinsic subtype and immune-related gene expression. sTIL levels increase after 2 weeks of HER2 blockade in HR-negative disease and HER2-enriched subtype. This is linked to a concomitant increase in cell density of all four immune subpopulations (CD3(+), CD4(+), CD8(+), Foxp3(+)). Moreover, immune contexture analysis showed that immune cells spatially interacting with tumour cells have the strongest association with response to anti-HER2 treatment. Subsequently, sTILs consistently decrease at the surgery in patients achieving pathologic complete response, whereas most residual tumours at surgery remain inflamed, possibly reflecting a progressive loss of function of T cells. Understanding the features of the resulting tumour immunosuppressive microenvironment has crucial implications for the design of new strategies to de-escalate or escalate systemic therapy in early-stage HER2+ BC.
Filiaciones:
Griguolo G:
Univ Padua, Dept Surg Oncol & Gastroenterol, Padua, Italy
Ist Oncol Veneto IRCCS, Div Oncol 2, Padua, Italy
August Pi i Sunyer Biomed Res Inst IDIBAPS, Translat Genom & Targeted Therapeut Solid Tumors, Barcelona, Spain
Serna G:
Vall dHebron Inst Oncol, Mol Oncol Grp, Barcelona, Spain
Pascual T:
August Pi i Sunyer Biomed Res Inst IDIBAPS, Translat Genom & Targeted Therapeut Solid Tumors, Barcelona, Spain
Hosp Clin Barcelona, Dept Med Oncol, Barcelona, Spain
SOLTI Breast Canc Res Grp, Barcelona, Spain
Fasani R:
Vall dHebron Inst Oncol, Mol Oncol Grp, Barcelona, Spain
Guardia X:
Vall dHebron Inst Oncol, Mol Oncol Grp, Barcelona, Spain
Chic N:
August Pi i Sunyer Biomed Res Inst IDIBAPS, Translat Genom & Targeted Therapeut Solid Tumors, Barcelona, Spain
Hosp Clin Barcelona, Dept Med Oncol, Barcelona, Spain
Pare L:
SOLTI Breast Canc Res Grp, Barcelona, Spain
Pernas S:
Inst Catala Oncol HU Bellvitge IDIBELL, Barcelona, Spain
Munoz M:
Hosp Clin Barcelona, Dept Med Oncol, Barcelona, Spain
Oliveira M:
Vall dHebron Univ Hosp, Med Oncol Dept, Barcelona, Spain
Vall dHebron Inst Oncol, Breast Canc & Melanoma Grp, Barcelona, Spain
Vidal M:
Hosp Clin Barcelona, Dept Med Oncol, Barcelona, Spain
Llombart-Cussac A:
Hosp Univ Arnau de Vilanova Valencia, Valencia, Spain
Cortes J:
IOB Inst Oncol, Quironsalud Grp, Madrid, Spain
IOB Inst Oncol, Quironsalud Grp, Barcelona, Spain
Galvan P:
August Pi i Sunyer Biomed Res Inst IDIBAPS, Translat Genom & Targeted Therapeut Solid Tumors, Barcelona, Spain
Bermejo B:
Hosp Clin Univ Valencia INCLIVA CIBERONC, Valencia, Spain
Martinez N:
Hosp Univ Ramon y Cajal, Madrid, Spain
Lopez R:
Hosp Clin Univ Santiago, CIBERONC, IDIS, Santiago De Compostela, Spain
Morales S:
Hosp Univ Arnau de Vilanova Lleida, Lleida, Spain
Garau I:
Hosp Son Llatzer, Palma De Mallorca, Spain
Manso L:
Hosp Univ 12 Octubre, Madrid, Spain
Alarcon J:
Hosp Univ Son Espases, Palma De Mallorca, Spain
Martinez E:
Consorcio Hosp Prov Castellon, Castellon de La Plana, Spain
Villagrasa P:
SOLTI Breast Canc Res Grp, Barcelona, Spain
Prat A:
August Pi i Sunyer Biomed Res Inst IDIBAPS, Translat Genom & Targeted Therapeut Solid Tumors, Barcelona, Spain
Hosp Clin Barcelona, Dept Med Oncol, Barcelona, Spain
SOLTI Breast Canc Res Grp, Barcelona, Spain
Nuciforo P:
Vall dHebron Inst Oncol, Mol Oncol Grp, Barcelona, Spain
SOLTI Breast Canc Res Grp, Barcelona, Spain
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